The long-term objective of the proposed studies is to evaluate the contribution of low and high pressure baroreceptors in the neurohumoral responses to simulated hypovolemia. Reduction in venous return leads to stimulation of renin, vasopressin and ACTH secretion and to drinking. These mechanisms, together with the sympathetic nervous system stabilize blood pressure and act synergistically to return fluid balance to normal. The overall hypothesis is that unloading baroreceptors in the left atrium is essential for the expression of these neurohumoral responses to simulated hypovolemia. Differential changes in pressure will be achieved by graded constriction of cuffs placed around the thoracic portion of the inferior vena cava, pulmonary artery, ascending aorta and abdominal aorta proximal to the renal arteries. The hypothesis that increases in left atrial, rather than left ventricular, pressure inhibit vasopressin, renin and ACTH secretion and drinking when arterial blood pressure is reduced by ascending aortic cuff constriction will be tested. Techniques of maintenance of normal left atrial pressures and selective ventricular denervation during aortic constriction will be used. The effects of raised right atrial pressure on the neurohumoral response to arterial hypotension will be evaluated using pulmonary artery constriction. Inflation of a balloon in the pulmonary vein/left atrium junctional region will be used to assess the effects of increasing afferent discharge without release of atrial natriuretic factor (ANF), and compared with inflation of a balloon placed at the mitral valve orifice which increases afferent discharge and ANF release. It is anticipated that both left atrial baroreceptors and ANF contribute to the inhibition of renin, vasopressin and ACTH release and drinking when left atrial pressure increases. The contribution of the sympathetic nervous system to inhibition of renin secretion when left atrial pressure increases will be assessed by measurement of plasma epinephrine and measurement of renal nerve activity. Thus it is anticipated that the essential role of the left atrium in hormonal and thirst responses to simulated hypovolemia will be established and that the mechanism of these interactions will be elucidated.